Glioblastoma in Elderly Patients: Current Management and Future Perspectives.

Giuseppe Lombardi,Giuseppe Minniti,Sergio Paolini

doi:10.3390/cancers11030336

Abstract

The incidence of glioblastoma (GBM) in the elderly population is slowly increasing in Western countries. Current management includes surgery, radiation therapy (RT) and chemotherapy; however, survival is significantly worse than that observed in younger patients and the optimal treatment in terms of efficacy and safety remains a matter of debate. Surgical resection is often employed as initial treatment for elderly patients with GBM, although the survival benefit is modest. Better survival has been reported in elderly patients treated with RT compared with those receiving supportive care alone, with similar survival outcome for patients undergoing standard RT (60 Gy over 6 weeks) and hypofractionated RT (25–40 Gy in 5–15 daily fractions). Temozolomide, an alkylating agent, may represent an effective and safe therapy in patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene which is predictor of responsiveness to alkylating agents. An abbreviated course of RT, 40 Gy in 15 daily fractions in combination with adjuvant and concomitant temozolomide has emerged as an effective treatment for patients aged 65 years old or over with GBM. Results of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG CE6) and European Organization for Research and Treatment of Cancer (EORTC 26062/22061) randomized study of short-course RT with or without concurrent and adjuvant temozolomide have demonstrated a significant improvement in progression-free survival and overall survival for patients receiving RT and temozolomide over RT alone, without impairing either quality of life or functional status. Although combined chemoradiation has become the recommended treatment in fit elderly patients with GBM, several questions remain unanswered, including the survival impact of chemoradiation in patients with impaired neurological status, advanced age (>75–80 years old), or for those with severe comorbidities. In addition, the efficacy and safety of alternative therapeutic approaches according to the methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter need to be explored in future trials.

Highlights

Gliomas account for almost 80% of all primary malignant brain tumors
The purpose of this review is to summarize the published literature on the efficacy of radiation therapy (RT) and chemotherapy given alone or in combination in elderly patients with GBM, and to address important issues such as the importance of molecular profiling in predicting response to treatments, the impact of treatments on quality of life and neurocognitive outcomes, and future research priorities for this population
For elderly patients with newly diagnosed GBM, current management includes surgery, RT and chemotherapy; survival is significantly worse than that observed in younger patients

Summary

Introduction

Glioblastoma (GBM) is the most frequent histology and accounts for more than 50% of gliomas in all age groups, with an incidence rate among elderly patients of 70 years and older of 17.5 per 100,000 person-years, and a relative risk of 3–4 times compared with young adults [1,2,3]. Considering that the population of 65 years or older is expected to increase in the two decades in USA, Canada, Australia, and Europe, this age group will account for the majority of GBM cases in these nations, representing an important aspect of public health. The majority of elderly patients with GBM are less likely to receive standard chemoradiation because aggressive combined approaches are associated with lower survival benefit and increased toxicity.

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